Polycystin-1 Activates PI3 Kinase/AKT Signaling. Expression of polycystin-1 in MDCK cells promotes tubulogenesis and confers resistance to apoptosis. Boca et al. examined the mechanism underlying these effects. They found that expression of wild-type polycystin-1, but not mutant polycystin-1, activates phosphatidylinositol 3-kinase (PI3-kinase) and stimulates the phosphorylation of Akt (protein kinase B) and its downstream target FKRH-1. Akt has previously been shown to stimulate tubulogenesis

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... nd inhibit apoptosis. Expression of a dominant-negative Akt mutant prevents the resistance to apoptosis conferred by polycystin-1. Treatment with PI3-kinase inhibitors blocks phosphorylation of Akt and inhibits tubulogenesis. Recent studies suggest that inhibition of calcium-dependent activation of PI3-kinase and Akt leads to activation of ERK kinases and increases cell proliferation. Taken together, these findings suggest that polycystin-1 may exert its cellular effects by promoting calcium entry and activating the PI3-kinase/Akt signaling pathway. In autosomal dominant polycystic kidney disease, loss of polycystin-1 results in inhibition of PI3-kinase/Akt, increased ERK, and increased proliferation and apoptosis. See Boca et al.,